The role of familial/parental factors in modulating youths? reactions to terrorism is supported by the scientific literature, including the Child Psychiatric Epidemiology Group?s (CPEG) findings from youth assessed six months after 9/11 (N=8,236; see Significance). Those findings led to a NICHD-funded grant (Wave 1-2 WTC Family Study) to understand the impact, over time, of parental direct WTC-exposure on their children?s psychopathology. For that study, N=855 families (parents + one child) of WTC First Responders, WTC Evacuees and local Residents were recruited from the World Trade Center Health Registry (WTCHR), as well as 9/11 unexposed Control families. The Wave 1-2 WTC Family Study was innovative and unique in that it: (a) examined the effects of direct exposure of parents to the consequential effect of indirect (?take home?) exposure on their children, (b) it followed families over time, and (c) assessed a broad array of psychiatric disorders in parents and children with DSM diagnostic instruments. Since initiation of the WTCHR and the Wave 1-2 WTC Family Study, NIMH developed the Research Domain Criteria (RDoC) project, a new way to classify mental disorders based on validated behavioral functions, supported by neural circuits. RDoC domains have quickly illuminated the conceptualization of psychopathology by providing a more comprehensive framework of functions/deficits across a spectrum of disorders and the health-illness dimension. This conceptualization is critical to understanding the long-term consequences to individuals and families with 9/11 exposure. Additionally, the explosion of high-throughput technologies has led to a more comprehensive view of the genetic architecture of observable behaviors and of gene-environment interactions (GE), which may be critical in the development of individualized treatment plans for 9/11 exposed individuals. To date, there has been no other 9/11 investigation that encompasses families, even of First Responder, WTC and Residential Evacuee families, the most adversely impacted WTC population. Based on findings from the Wave 1-2 WTC Family Study on the effects of parental WTC-exposure/psychiatric disorders on their child?s? psychopathology, as well as other epidemiological, behavioral and genetic findings by CPEG regarding these individuals (see Approach-C.4), we propose to follow-up the same families for a 3rd wave, to examine how four key RDoC domains of functioning (negative valence; positive valence; cognitive systems; social cognition) are associated upward with (i) long-term psychiatric outcomes (DSM disorders), (ii) emotional health (psychological resilience), and (iii) trajectories of psychopathology, and downward, with interactions between genetic variation and direct/indirect WTC exposures.